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In 1931, physicist Ernst Ruska—building on the idea that magnetic fields can direct an electron beam just as lenses can direct a beam of light in an optical microscope—developed the first prototype of the electron microscope. This development led to the development of the field of electron microscopy. In the transmission electron microscope (TEM), electrons are produced by a hot tungsten element and accelerated by a potential difference in an electron gun, which gives them up to 400...
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Immunoelectron microscopy utilizes immunogold labeling of endogenous proteins with specific antibodies to detect and localize these proteins in cells and tissues. The procedure provides insights into the distribution and quantification of protein under different stimulation conditions offering clues about their functions. Conjugating highly electron-dense gold particles with primary or secondary antibodies allow antigen detection on and within cells, with high resolution and specificity.
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Transmission Electron Microscopy of the Peripheral Nervous System: Methods, Sample Preparation, and Case Studies.

Agnieszka Collins1, Christopher Hayden2, Emily K Meseck3

  • 1Novartis Biomedical Research, Cambridge, Massachusetts, USA.

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|November 18, 2025
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Summary

This guide details best practices for collecting and preparing peripheral nerve and ganglion samples for microscopy. It highlights transmission electron microscopy (TEM) uses and limitations in nonclinical safety studies for pharmaceutical development.

Keywords:
dorsal root gangliaperipheral nervous systemspinal sensory gangliatransmission electron microscopyultrastructural pathology

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Area of Science:

  • Neuroscience
  • Pathology
  • Microscopy

Background:

  • Peripheral nerves and ganglia are crucial for evaluating drug safety.
  • Standardized methods for their ultrastructural analysis are essential for accurate pathology assessment.
  • Emerging pharmaceutical modalities require robust nonclinical safety data.

Purpose of the Study:

  • To provide practical recommendations for peripheral nerve and ganglion sample processing.
  • To illustrate the utility and limitations of transmission electron microscopy (TEM) in nonclinical safety evaluations.
  • To identify common artifacts and findings in nerve and ganglion ultrastructure.

Main Methods:

  • Detailed protocols for sample collection, fixation, and resin embedding.
  • Light microscopy and transmission electron microscopy (TEM) techniques for ultrastructural evaluation.
  • Case studies using control and test article-dosed nonclinical samples.

Main Results:

  • Established best practices for high-quality ultrastructural preservation.
  • Demonstrated common artifacts (e.g., swelling, myelin defects) and pathological findings.
  • Highlighted the value of TEM in detecting subtle nerve and ganglion changes.

Conclusions:

  • Standardized sample preparation enhances the reliability of ultrastructural pathology.
  • TEM is a valuable tool for nonclinical safety assessment of peripheral nerves and ganglia.
  • Understanding artifacts is critical for accurate interpretation of TEM findings in drug development.